Recent advances in the treatment and monitoring of HIV infection have substantially reduced rates of HIV-associated illness and mortality;however, the management of HIV-infected patients has become increasingly complex. We are conducting studies to (1) evaluate novel therapeutic strategies for managing hepatitis C virus (HCV) infection in HIV-co-infected individuals, and (2) identify critical host factors that can predict an HIV-infected individuals response to existing HCV treatments and/or future therapies. This past year, we (1) determined the safety, tolerability and effectiveness of a novel regimen of twice monthly albumin-interferon alpha 2b plus ribavirin to treat Hepatitis C in HIV co-infected individuals;(2) demonstrated the distinct influence of ongoing HIV replication on host immune activation profiles in patients co-infected with Hepatitis C;(3) demonstrated the effect of race and baseline immune status (CD4+ T-cell count) on response rates to HCV therapy using pegylated interferon-alpha and ribavirin, (4) evaluated novel anti-HCV agents (IL-27, IL-28 and IL-29) in vitro using a newly developed HCV continuous culture system, and (5) demonstrated the role of individual Interferon-inducible gene products in controlling HCV replication in vitro.